Phase 4 COPD and Suboptimal Inspiratory Flow Rate

Chronic Obstructive Pulmonary Disease Clinical Trial

— PIFR-2  

Official title:

A Phase 4, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Study Comparing Improvements in Lung Function in Adults With Severe to Very Severe Chronic Obstructive Pulmonary Disease and Suboptimal Inspiratory Flow Rate Following Once-Daily Treatment Over 12 Weeks With Either Revefenacin Inhalation Solution Delivered Via Standard Jet Nebulizer or Tiotropium Delivered Via a Dry Powder Inhaler (Spiriva® HandiHaler®)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05165485
• Other study ID #: 0180
• Status: Completed
• Phase: Phase 4
• Start date: January 7, 2022
• Est. completion date: November 20, 2023

Study information

• Verified date: December 2023
• Source: Theravance Biopharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study is a randomized, double-blind, double-dummy, parallel-group study evaluating efficacy and safety of revefenacin vs. tiotropium in adults with severe to very severe COPD and suboptimal PIFR.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. completion date: November 20, 2023
• Est. primary completion date: November 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

1. Participant is a male or female 40 years of age or older.

2. Participant is female and is nonpregnant and nonlactating. A woman of childbearing potential must have a documented negative urine pregnancy test at screening. Women are considered not to be of childbearing potential if they have had a total hysterectomy and/or bilateral tubal ligation (documentation for either must be provided before enrollment) or are at least 2 years postmenopausal.

3. During the study and for 30 days after receiving the last dose of study drug, women of childbearing potential and men capable of fathering children must agree to use highly effective birth control measures or agree to abstain from sexual intercourse.

A highly effective method of birth control is defined as one that results in a low failure rate (i.e. <1% per year) when used consistently and correctly, such as condom + diaphragm, condom + spermicide, diaphragm + spermicide, or intrauterine device [IUD] with documented failure rate of <1% per year, or oral/injectable/implanted hormonal contraceptives used in combination with an additional barrier method.

4. Participant has a diagnosis of COPD, specifically, a post-ipratropium FEV1/FVC ratio <0.7.

5. Participant has a post ipratropium 30% = FEV1 < 50% of predicted normal (using National Health and Nutrition Examination Survey-predicted equations) and absolute FEV1 > 500 mL, or FEV1 <30% predicted normal and absolute FEV1 > 700 mL.

6. Participant has a PIFR <60 L/min as measured by an In-Check™ device with resistance set to DISKUS at Visit 1A (if not combined with Visit 1B) and < 55 L/min as measured by an In-Check™ device with resistance set to DISKUS at Visit 1B and Visit 2 prior to randomization.

7. Participant is capable of performing reproducible spirometry maneuvers (and plethysmography maneuvers for a subset of participants) as described by current American Thoracic Society (ATS) Guidelines.

8. Participant is an active or former smoker with a cigarette smoking history (or equivalent for cigar or pipe smoking history) of at least 10 pack-years.

9. Participant or legal guardian is willing and able to provide signed and dated informed consent to participate prior to initiation of any study related procedures.

10. Participant is willing and able to adhere to all study assessments/procedures. Care partner assistance is acceptable.

11. Participant is willing and able to adhere to all restrictions during their study participation as follows:

• Use of recreational drugs

• Medicinal marijuana

• Excessive alcohol during the study period

• Participation in another investigational drug study

• Donation of =500 mL blood (or equivalent)

12. Participant (or care partner) based on the investigator's assessment is able to properly prepare and administer study medication administered from both nebulizer and HandiHaler® according to their respective Instructions for Use.

Exclusion Criteria:

1. Participant has a concurrent disease or condition that, in the opinion of the investigator, would interfere with study participation or confound the evaluation of safety and tolerability of the study drug.

2. Participant has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergics.

3. Participant suffers from any medical condition that would preclude the use of inhaled anticholinergics, including narrow-angle glaucoma, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or urinary retention.

4. Participant has Moderate to Severe Hepatic impairment (Child-Pugh B or C) or Severe Renal Insufficiency (i.e. a glomerular filtration rate <30 mL/min/1.72m2).

5. Participant has been hospitalized for COPD or pneumonia within 8 weeks prior to Visit 1.

6. Participant is receiving a LABA or LABA/inhaled corticosteroid (ICS; either QD or BID) at a dose that has been stable for = 30 days prior to screening.

7. Participant has used systemic corticosteroids within 8 weeks of Visit 1.

8. Participant has used antibiotics for respiratory tract infections within 8 weeks of Visit 1, or is using antibiotics prophylactically.

9. Participant received COVID-19 vaccine within 2 weeks prior to Visit 1.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Respiratory Aspiration

Intervention

Drug:
• Revefenacin
Revefenacin DoseA
• Tiotropium
Tiotropium DoseB
• Revefenacin Placebo
Placebo for Revefenacin administered with Tiotropium
• Tiotropium Placebo
Placebo for Tiotropium administered with Revefenacin

Locations

Country	Name	City	State
United States	Theravance Biopharma Investigational Site	Anderson	South Carolina
United States	Theravance Biopharma Investigational Site	Charlotte	North Carolina
United States	Theravance Biopharma Investigational Site	Cincinnati	Ohio
United States	Theravance Biopharma Investigational Site	Clearwater	Florida
United States	Theravance Biopharma Investigational Site	Clearwater	Florida
United States	Theravance Biopharma Investigational Site	Columbia	South Carolina
United States	Theravance Biopharma Investigational Site	Columbus	Ohio
United States	Theravance Biopharma Investigational Site	Farmington Hills	Michigan
United States	Theravance Biopharma Investigational Site	Franklin	Tennessee
United States	Theravance Biopharma Investigational Site	Gaffney	South Carolina
United States	Theravance Biopharma Investigational Site	Grants Pass	Oregon
United States	Theravance Biopharma Investigational Site	Greenville	South Carolina
United States	Theravance Biopharma Investigational Site	Jasper	Alabama
United States	Theravance Biopharma Investigational Site	Knoxville	Tennessee
United States	Theravance Biopharma Investigational Site	Las Vegas	Nevada
United States	Theravance Biopharma Investigational Site	Leesburg	Florida
United States	Theravance Biopharma Investigational Site	Lexington	South Carolina
United States	Theravance Biopharma Investigational Site	Medford	Oregon
United States	Theravance Biopharma Investigational Site	Miami	Florida
United States	Theravance Biopharma Investigational Site	Miami	Florida
United States	Theravance Biopharma Investigational Site	Monroe	North Carolina
United States	Theravance Biopharma Investigational Site	North Charleston	South Carolina
United States	Theravance Biopharma Investigational Site	North Dartmouth	Massachusetts
United States	Theravance Biopharma Investigational Site	Orlando	Florida
United States	Theravance Biopharma Investigational Site	Ormond Beach	Florida
United States	Theravance Biopharma	Phoenix	Arizona
United States	Theravance Biopharma Investigational Site	Portland	Oregon
United States	Theravance Biopharma Investigational Site	Raleigh	North Carolina
United States	Theravance Biopharma Investigational Site	Rock Hill	South Carolina
United States	Theravance Biopharma Investigational Site	Saint Charles	Missouri
United States	Theravance Biopharma Investigational Site	San Antonio	Texas
United States	Theravance Biopharma Investigational Site	Sarasota	Florida
United States	Theravance Biopharma Investigational Site	Sherman	Texas
United States	Theravance Biopharma Investigational Site	Spartanburg	South Carolina
United States	Theravance Biopharma Investigational Site #2	Spartanburg	South Carolina
United States	Theravance Biopharma Investigational Site	Tampa	Florida
United States	Theravance Biopharma Investigational Site	Union	South Carolina
United States	Theravance Biopharma Investigational Site	Valparaiso	Indiana
United States	Theravance Biopharma Investigational Site	Winter Park	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Theravance Biopharma	Viatris Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FEV1	Change from baseline in trough FEV1	Day 85 following 84 days of dosing
Secondary	OTE on FEV1	Trough Overall treatment effect (OTE) on FEV1	Day 30 through Day 85
Secondary	FEV1	Change from baseline in Trough FEV1 on Day 30	Day 30
Secondary	FEV1	Change from baseline in Trough FEV1 on Day 60	Day 60
Secondary	FVC	Change from baseline in Trough FVC	Day 85
Secondary	80-mL improvement in trough FEV1	Percentage of participants who achieve at least an 80-mL improvement in trough FEV1	Day 85
Secondary	Time to first CompEx	Composite endpoint for exacerbations of COPD event	Baseline through Day 85